Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC).

Cancers of the head & neck Pub Date : 2018-06-04 eCollection Date: 2018-01-01 DOI:10.1186/s41199-018-0030-z
Kyungsuk Jung, Hyunseok Kang, Ranee Mehra
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引用次数: 61

Abstract

The landscape of head and neck squamous cell carcinoma (HNSCC) has been changing rapidly due to growing proportion of HPV-related disease and development of new therapeutic agents. At the same time, there has been a constant need for individually tailored treatment based on genetic biomarkers in order to optimize patient survival and alleviate treatment-related toxicities. In this regard, aberrations of PI3K pathway have important clinical implications in the treatment of HNSCC. They frequently constitute 'gain of function' mutations which trigger oncogenesis, and PI3K mutations can also lead to emergence of drug resistance after treatment with EGFR inhibitors. In this article, we review PI3K pathway as a target of treatment for HNSCC and summarize PI3K/mTOR inhibitors that are currently under clinical trials. In light of recent advancement of immune checkpoint inhibitors, consideration of PI3K inhibitors as potential immune modulators is also suggested.

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靶向磷酸肌肽3激酶(PI3K)在头颈部鳞状细胞癌(HNSCC)中的作用。
头颈部鳞状细胞癌(HNSCC)的前景已经迅速改变,由于hpv相关疾病的比例不断增加和新的治疗药物的发展。与此同时,一直需要基于遗传生物标志物的个性化治疗,以优化患者生存并减轻治疗相关的毒性。因此,PI3K通路的畸变在HNSCC的治疗中具有重要的临床意义。它们经常构成触发肿瘤发生的“功能获得”突变,PI3K突变也可能导致EGFR抑制剂治疗后出现耐药性。在本文中,我们回顾了PI3K途径作为治疗HNSCC的靶点,并总结了目前正在临床试验中的PI3K/mTOR抑制剂。鉴于免疫检查点抑制剂的最新进展,也建议考虑PI3K抑制剂作为潜在的免疫调节剂。
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